STOCK Tpp1^m1J/GrsrJ

Stock number: 012876
Research areas: Neurobiology Research

Description

This ENU-induced point mutation in non-coding sequence provides a strong model for late-infantile neuronal ceroid lipofuscinosis without the caveats associated with neomycin phosphotransferase.

Detailed description

Homozyogtes can be phenotypically identified by a tremor and hunched posture by 3.5 to 4 months of age. The tremor is intermittent and more pronounced when walking. The tremor, ataxia, and diminished locomotion progress and homozygotes die by 6 months of age. Myelin figures in the white matter, and eosinophilic and luxol fast blue positive neuronal inclusions are found, but retinal degeneration and diminished electroretinogram readings are not found. The molecular defect is a T to C point mutation in a splice donor site just downstream of exon 8. While this is a good model for late-infantile neuronal ceroid lipofuscinosis, the lack of an ocular phenotype differs from the disease in human.

Development

The Tpp1^m1J mutation was identified in the progeny of an ENU treated C57BL/6J, which was part of a region-specific mutagenesis screen in the laboratory of Dr. Simon John. The mutagenized C57BL/6J male was bred to C3Fe.Cg-Rw heterozygous females, and a male F1 offspring that was heterozygous for Rw and any ENU-induced mutations was bred to a C3Fe.Cg-Hm +/+ Rw female. One of their female offspring heterozygous for Rw and any inherited ENU-induced mutations was backcrossed to its F1 father (also heterozygous for Rw and any ENU-induced mutations). The recessive Tpp1^m1J mutation was identified in their progeny and this mutant was used to propagate a line that was sibling inbred to homozygosity. At F18 this line was outcrossed once to C57BL/6J and then again intercrossed to homozygosity, reaching generation F18N1F12 in 2013. Thus, this STOCK background consists predominantly of C57BL/6J and C3HeB/FeJ with possible trace contributions from C3H/HeH, 101/H and other undefined backgrounds.

Allele

Symbol: Tpp1^m1J
Name: mutation 1, Jackson
MGI accession ID: MGI:5512906
Generation method: Chemically induced (ENU)
Marker symbol: Tpp1
Marker name: tripeptidyl peptidase I
Chromosome: 7
Strain of origin: C57BL/6J
Molecular note: A single T-to-C (A-to-G on forward strand) transition at position 105,748,881 (GRCm38) in chromosome 7 alters exon 8 splice donor site from G-GT to G-GC.